The work proposed here is designed to define the role of the membrane in the survival and function of red blood cells. The role of the membrane lipid peroxidation in accelerating premature cell lysis will be studied by determination of the susceptibility of normal and pathologic red cells to peroxidation, measurement of physical and chemical changes in red cells occurring after peroxidation, efforts to determine red cell peroxidation in vitro in pathologic conditions, and the measurement of the effects of in vitro peroxidation on the survival of human erythrocytes with an in vivo animal model. In addition, the role of the membrane protein kinase system and its substrates in the regulation of cell shape and membrane function will be studied. This work will include a detailed examination of the properties of spectrin, a series of studies of membrane: macromolecular interactions, and a series of studies on the phosphorylation of membrane protein. These latter experiments will utilize membranes from normal cells, normal maturing reticulocytes, and hereditary spherocytosis cells of both mice and men.